Capisterones A and B, which enhance fluconazole activity in Saccharomyces cerevisiae, from the marine green alga Penicillus capitatus.

Journal of Natural Products
Xing-Cong LiAlice M Clark

Abstract

A whole-cell-based assay using Saccharomyces cerevisiae strains that overexpress Candida albicans CDR1 and MDR1 efflux pumps has been employed to screen natural product extracts for reversal of fluconazole resistance. The tropical green alga Penicillus capitatus was selected for bioassay-guided isolation, leading to the identification of capisterones A and B (1 and 2), which were recently isolated from this alga and shown to possess antifungal activity against the marine pathogen Lindra thallasiae. Current work has assigned their absolute configurations using electronic circular dichroism and determined their preferred conformations in solution based on detailed NOE analysis. Compounds 1 and 2 significantly enhanced fluconazole activity in S. cerevisiae, but did not show inherent antifungal activity when tested against several opportunistic pathogens or cytotoxicity to several human cancer and noncancerous cell lines (up to 35 microM). These compounds may have a potential for combination therapy of fungal infections caused by clinically relevant azole-resistant strains.

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Citations

Sep 24, 2008·Journal of Natural Products·Xiang FuIkhlas A Khan
Feb 6, 2008·Natural Product Reports·John W BluntMichèle R Prinsep
Aug 28, 2010·American Journal of Pharmaceutical Education·Jack E Fincham
Aug 17, 2011·Evidence-based Complementary and Alternative Medicine : ECAM·Rosa Moo-PucYolanda Freile-Pelegrin
Jan 1, 2010·Saudi Pharmaceutical Journal : SPJ : the Official Publication of the Saudi Pharmaceutical Society·Ali A El Gamal
Jul 28, 2016·Future Medicinal Chemistry·Ann R HolmesRichard D Cannon
Jan 5, 2018·Journal of Molecular Endocrinology·Francisca CarvalhalAnake Kijjoa
Nov 23, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Bahare SalehiNatália Martins

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